1.
High-Density Lipoprotein Reduction Differentially Modulates to Classical and Nonclassical Monocyte Subpopulations in Metabolic Syndrome Patients and in LPS-Stimulated Primary Human Monocytes In Vitro.
Grün, JL, Manjarrez-Reyna, AN, Gómez-Arauz, AY, Leon-Cabrera, S, Rückert, F, Fragoso, JM, Bueno-Hernández, N, Islas-Andrade, S, Meléndez-Mier, G, Escobedo, G
Journal of immunology research. 2018;:2737040
Abstract
The effect of metabolic syndrome on human monocyte subpopulations has not yet been studied. Our main goal was to examine monocyte subpopulations in metabolic syndrome patients, while also identifying the risk factors that could directly influence these cells. Eighty-six subjects were divided into metabolic syndrome patients and controls. Monocyte subpopulations were quantified by flow cytometry, and interleukin- (IL-) 1β secretion levels were measured by ELISA. Primary human monocytes were cultured in low or elevated concentrations of high-density lipoprotein (HDL) and stimulated with lipopolysaccharide (LPS). The nonclassical monocyte (NCM) percentage was significantly increased in metabolic syndrome patients as compared to controls, whereas classical monocytes (CM) were reduced. Among all metabolic syndrome risk factors, HDL reduction exhibited the most important correlation with monocyte subpopulations and then was studied in vitro. Low HDL concentration reduced the CM percentage, whereas it increased the NCM percentage and IL-1β secretion in LPS-treated monocytes. The LPS effect was abolished when monocytes were cultured in elevated HDL concentrations. Concurring with in vitro results, IL-1β serum values significantly increased in metabolic syndrome patients with low HDL levels as compared to metabolic syndrome patients without HDL reduction. Our data demonstrate that HDL directly modulates monocyte subpopulations in metabolic syndrome.
2.
Upregulation of monocyte tissue factor activity is significantly associated with carotid intima-media thickness in patients with metabolic syndrome.
Nakagomi, A, Sasaki, M, Ishikawa, Y, Shibui, T, Kosugi, M, Endoh, Y, Morikawa, M, Kusama, Y, Atarashi, H, Mizuno, K
Journal of atherosclerosis and thrombosis. 2011;(6):475-86
Abstract
AIMS: Metabolic syndrome (MS) represents a cluster of cardiovascular risk factors and an increased risk of cardiovascular events. The carotid intima-media thickness (CIMT) is correlated with coronary and carotid atherosclerosis, and is a significant predictor of cardiovascular events. Tissue factor (TF) is an initiator of the extrinsic coagulation cascade and is expressed on peripheral blood monocytes and macrophages in atherosclerotic plaques. TF plays important roles in both thrombosis and atherosclerosis. No study has investigated the relationship between monocyte TF activity and CIMT in MS patients. METHODS Peripheral blood mononuclear cells (PBMCs) were collected from 39 normal subjects and 110 patients with MS. The procoagulant activity (PCA) in monocytes was measured using a one-stage clotting assay and is expressed as the mean±SD (mU TF/10(6) PBMCs). RESULTS The PCA in monocytes in MS patients was significantly higher than in normal subjects (86.2 ±69.5 vs. 52.4±9.9 mU TF/10(6) PBMCs, p < 0.001). In multivariate analysis, patient age (β coefficient= 0.373, p < 0.001), high-density lipoprotein cholesterol (β coefficient=-0.307, p = 0.001) and PCA (β coefficient= 0.422, p =0.002) were each significantly and independently associated with CIMT. CONCLUSIONS These data indicate that the upregulation of monocyte TF activity is significantly associated with CIMT in MS patients.
3.
Metabolic syndrome abating the beneficial effect of pravastatin treatment on adhesion of endothelium by monocytes in subjects with hypercholesterolemia.
Lee, IT, Lee, WJ, Ou, HC, Huang, CN, Sheu, WH
Metabolism: clinical and experimental. 2009;(3):416-20
Abstract
Statin, a potent lipid-lowering agent, ameliorates the interaction of monocytes and endothelium, a critical step in the atherosclerotic process. However, it remains unclear whether this effect of statin depends on different doses or the presence of metabolic syndrome. In this prospectively double-blind study, 21 hypercholesterolemia subjects, with low-density lipoprotein cholesterol between 130 and 170 mg/dL, received low-dose (10 mg/d) or high-dose (40 mg/d) pravastatin treatment for 8 weeks. We assessed the reduction of monocyte adhesion to cultured endothelium between different-dose groups and the relationship to metabolic syndrome. Total cholesterol and low-density lipoprotein cholesterol were significantly decreased after 40-mg pravastatin treatment (-23.3% +/- 3.7%, P < .001 and -28.8% +/- 3.0%, P < .001), and the reductions were greater than those in the 10-mg group (P = .041 and P = .045, respectively). There was no significant difference in monocyte adhesion between high-dose and low-dose pravastatin treatment. When all subjects were divided into an improvement group and a no improvement group, according to the median of change percentage of monocyte adhesion after pravastatin treatment, there were significantly more subjects with metabolic syndrome in the no improvement than the improvement group (6 vs 1 person, P =.024). Using logistic regression analysis, metabolic syndrome, rather than dose effect of pravastatin, was an independent predictor of interaction between monocytes and endothelium (95% confidence interval = 0.001-0.865, P = .041). Attenuating adhesion between monocytes and endothelium is altered by the presence of metabolic syndrome when hypercholesterolemia subjects receive pravastatin treatment.